In recent years a number delivery systems comprised of a biocompatible polymer and a drug for treating a particular disease or condition have been produced. Polymeric drug delivery systems include implantable devices, such as stents, that are implanted into particular regions of the body for localized delivery of the drug. Polymeric drug delivery systems also include specific geometrics such as for example, microspheres, nanospheres, and cylinders that are injected through a needle into the body of the patient, e.g. into a muscle or the blood stream. The particles are injected into the blood stream for systemic delivery or delivery to a specific site. Targeted delivery to a specific site maximizes drug action and minimizes side effects. The ability to minimize side effects is especially important in cancer chemotherapy, vaccine delivery, and diagnostic imaging.
In order to target polymeric particles to a particular tissue or region of the body, it is necessary to include functional groups, such as ligands and antibodies, on the surface of the polymeric particle. Functional groups are also included on the surface of polymeric particle to avoid clearance by the reticuloendothelial system (RES) Without such groups, sufficient quantities of the particles may not reach the targeted tissue or site. In certain cases, bioactive molecules, such as peptide vaccines and genes, may also be attached to the surface of polymeric particles.
Attempts have been made to attach functional groups or bioactive molecules to the polymeric particle by modifying the biocompatible polymers themselves. The most successful methods that are currently employed involve covalently linking conjugatable or ligatable groups to the biocompatible polymer (e.g. to form a block copolymer) prior to formation of the polymeric particle. Such methods result in the formation of a modified polymer or copolymer which, unfortunately, does not have the same physical bulk properties as the unmodified polymer. Such methods are also expensive, inefficient, and time consuming.
Accordingly, it is desirable to have new methods of making biocompatible polymeric delivery systems that have functional groups, including conjugatable groups, on the surface thereof.